Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
Oncol Rep. 2013 Apr;29(4):1343-8. doi: 10.3892/or.2013.2252. Epub 2013 Jan 24.
Matrix metalloproteinases (MMPs) play an important role in cancer metastasis, cell migration and invasion. Herein, we investigated the effects of silibinin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and MMP-9 expression in thyroid and breast cancer cells. Our results revealed that the levels of MMP-9 mRNA and protein expression were significantly increased by TPA but not MMP-2 in TPC-1 and MCF7 cells. To verify the regulatory mechanism of TPA-induced MMP-9 expression, we treated TPC-1 and MCF7 cells with the MEK1/2 inhibitor, UO126, and TPA-induced MMP-9 expression was significantly decreased. We also found that TPA-induced cell migration and MMP-9 expression was significantly decreased by silibinin. In addition, TPA-induced phosphorylation of MEK and ERK was also inhibited by silibinin. Taken together, we suggest that silibinin suppresses TPA-induced cell migration and MMP-9 expression through the MEK/ERK-dependent pathway in thyroid and breast cancer cells.
基质金属蛋白酶(MMPs)在癌症转移、细胞迁移和侵袭中发挥重要作用。在此,我们研究了水飞蓟素对 12-O-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的甲状腺和乳腺癌细胞迁移和 MMP-9 表达的影响。我们的结果表明,TPA 可显著增加 MMP-9 mRNA 和蛋白表达水平,但对 MMP-2 无影响,在 TPC-1 和 MCF7 细胞中。为了验证 TPA 诱导 MMP-9 表达的调节机制,我们用 MEK1/2 抑制剂 UO126 处理 TPC-1 和 MCF7 细胞,发现 TPA 诱导的 MMP-9 表达显著降低。我们还发现,水飞蓟素可显著抑制 TPA 诱导的细胞迁移和 MMP-9 表达。此外,水飞蓟素还抑制了 TPA 诱导的 MEK 和 ERK 磷酸化。综上所述,我们认为水飞蓟素通过甲状腺和乳腺癌细胞中的 MEK/ERK 依赖性途径抑制 TPA 诱导的细胞迁移和 MMP-9 表达。